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Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis

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Abstract

Skin sensitization remains a major environmental and occupational health hazard. Animal models have been used as the gold standard method of choice for estimating chemical sensitization potential. However, a growing international drive and consensus for minimizing animal usage have prompted the development of in vitro methods to assess chemical sensitivity. In this paper, we examine existing approaches including in silico models, cell and tissue based assays for distinguishing between sensitizers and irritants. The in silico approaches that have been discussed include Quantitative Structure Activity Relationships (QSAR) and QSAR based expert models that correlate chemical molecular structure with biological activity and mechanism based read-across models that incorporate compound electrophilicity. The cell and tissue based assays rely on an assortment of mono and co-culture cell systems in conjunction with 3D skin models. Given the complexity of allergen induced immune responses, and the limited ability of existing systems to capture the entire gamut of cellular and molecular events associated with these responses, we also introduce a microfabricated platform that can capture all the key steps involved in allergic contact sensitivity. Finally, we describe the development of an integrated testing strategy comprised of two or three tier systems for evaluating sensitization potential of chemicals.

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Abbreviations

ACD:

Allergic Contact Dermatitis

BBB:

Blood Brain Barrier

BgVV:

Bundesinstitut für Gesundheitlichen Verbraucherschutz Und Veterinärmedizin

DC:

Dendritic Cells

DEREK:

Deductive Estimation of Risk from Existing Knowledge

DNCB:

DiNitroChloroBenzene

DNFB:

1-Fluoro-2,4-dinitrobenzene

DPRA:

Direct Peptide Reactivity Assay

GPMT:

Guinea Pig Maximization Test

h-CLAT:

human Cell Line Activation Test

HE-PPD:

Hydroxyethyl-p-phenylenediamine

HRIPT:

Human Repeated Insulin Patch Test

HRP/HP:

Horseradish Peroxidase/Hydrogen Peroxide

ITS:

Integrated Testing Strategies

LC:

Langerhans Cells

LR:

Linear Regression

LLNA:

Local Lymph Node Assay

MUSST:

Myeloid U937 Skin Sensitisation Test

MULTICASE:

Multiple Computer Automated Structure Evaluation

NCHS:

National Center for Health Statistics

OECD:

Organization for Economic Cooperation and Development

PCA:

Principal Component Analysis

PTD:

p-toluylenediamine

QSAR:

Quantitative Structure Activity Relationship

QSPR:

Quantitative Structure Property Relationship

REACh:

Registration, Evaluation, Authorization of Chemicals

SAR:

Structure Activity Relationship

TIMES-SS:

TImes MEtabolism Simulator platform used for predicting Skin Sensitization

TNCB:

2,4,6-Trinitrochlorobenzene

TOPKAT:

Toxicity Prediction by Komputer Assisted Technology

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  1. Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, 231, Piscataway, NJ, 08854, USA

    Nripen S. Sharma, Rohit Jindal, Bhaskar Mitra, Serom Lee, Lulu Li, Tim J. Maguire, Rene Schloss & Martin L. Yarmush

  2. Center for Engineering in Medicine, Massachusetts General Hospital, Boston, MA, 02114, USA

    Martin L. Yarmush

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Nripen S. Sharma and Rohit Jindal have contributed equally to this work.

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Sharma, N.S., Jindal, R., Mitra, B. et al. Perspectives on Non-Animal Alternatives for Assessing Sensitization Potential in Allergic Contact Dermatitis. Cel. Mol. Bioeng. 5, 52–72 (2012). https://doi.org/10.1007/s12195-011-0189-4

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